The metabolism of amino acids by the liver represents a major function of this tissue, yet the hepatic transport systems for these nutrients have for the most part not been well characterized. The present proposal seeks to continue the analysis of the transport processes and their regulation by hormones. A basic understanding of the hepatic transport systems which exist, their individual properties and their interaction with other membrane functions, is essential before further significance can be given to their role in metabolic disorders. Alloxandiabetic rats exhibit a stimulated uptake of amino acids by the liver, a possible contributing factor to the hyperglycemia and ketosis that develops. As a result the regulation of transport by the pancreatic hormones, insulin and glucagon, becomes extremely important. Isolated hepatocytes, Kupfer cells, and liver plasma membrane vesicles can be used to determine the amino acid transport systems present in liver tissue, the response of these systems to hormones and disease states, and the mechanism of coupling between hormone action and regulation of transport. The hepatocyte has been shown to contain three unique areas on its plasma membrane surface, namely the blood sinusoidal, the contiguous, and the bile canalicular. The composition, morphology, and enzymology of these three areas are distinguishable and have aided in the assignment as to location on the cell. Given that the polypeptide hormones are presented to the cell via the blood and the content of amino acids in the bile fluid is quite low, the regulation of transport in the three regions of the plasma membrane may be significantly different. If demonstrated, these differences can aid in our understanding of membrane structure-function relationships.